The development of scanning tunneling and atomic force microscopes has led to various kinds of applications. Examples of these applications are: scanning probe storage systems, e.g. storage systems making use of parallel local probes, scanning probe lithography systems, test equipment comprising a scanning probe or array of probes, atomic resolution, high throughput inspection systems, and scanning probe system used for the structuring of surfaces such as semiconductor chips and the like. All these systems have in common that they comprise one or more cantilevers.
Increasing efforts have been put into the development of cantilever-based sensors for the detection of physical phenomena and bio/chemical reactions.
Examples are the calorimetric sensor, also referred to as chemical nose, described in European Patent EP 711410 B1, or the spectroscopic measurement system described in U.S. Pat. No. 5,737,086.
The international application with publication no. WO 98 50773 describes a biosensor that includes a cantilever microbeam which responds to a chemical stimulus, binding event or mass loading with an electrical output. The microbeam is formed using a series of microfabrication processes, in the micrometer to millimeter size range and using thin deposition of piezoelectric materials. It is further described that a reference sensor, which lacks a biomolecular recognition surface, defines the baseline or index resonant frequency of the beam structure(s). A second sensor (test sensor) containing the specific biomolecular recognition surface is oscillated in a same fluid environment, is permitted to react with the cognate analyte, through a mass loading event. The consequent resonant frequency of the test is measured.
U.S. Pat. No. 5,807,758 describes a method and apparatus for detecting a target species. The target molecule may be in liquid phase (in solution) or (for some embodiments of the invention) in vapor phase. A sensor according to the invention monitors whether a target species has selectively bound to groups on the cantilever surface by monitoring the displacement of the cantilever, and hence the force acting on the cantilever. This force acting on the cantilever arises from the force acting on a structure that moves in electric or magnetic field, and that may be selectively bound to the cantilever. In the case of target species having a sufficiently large net electric charge or dipole moment, the target species itself may serve as the structure that moves in an electric field. More typically however, separate modified structures, such as modified magnetic beads or modified beads having a net charge or a dipole moment, will, when selectively bound to the cantilever, exert a force on the cantilever that relates to the presence of the target species.
In the article ‘An artificial nose based on a micromechanical cantilever array’ by LANG H. P. ET AL. In ANALYTICAL CHIMICA ACTA, vol. 393, no. 1-3, 30 Jun. 1999, pages 59-65, ISSN: 0003-2670, is described a chemical sensor based on a micromechanical array of silicon cantilevers. The article gives an overview of operation principles of cantilever-based sensors. It is mentioned that the use of an array of cantilever sensors allows some of the cantilevers to serve as reference sensors, i.e. sensors that do not react with the analyte. Thus, a small sensor response can be extracted in noisy environment.
The article ‘A high-sensitivity micromachined biosensor’ by BASELT D. R. ET AL. in PROCEED. IEEE, vol 85, no. 4, 1997, pages 672-680, describes a Force Amplified Biological Sensor (FABS). Each FABS cell currently contains two side-by-side Helmholtz pairs, one for a signal cantilever and one for a reference. To cancel out noise from external vibrations, FABS uses a reference cantilever that is identical to the signal cantilever except that it does not have an antibody coating.
It is a disadvantage of known micromechanical sensor systems for recognition of target substances or detection of properties of liquids that the results are difficult to reproduce since there is a strong dependence on environmental parameters. It is another disadvantage of known schemes that they are very sensitive to temperature fluctuations, pH changes and the like. Recognition of atoms or molecules is thus very difficult if not impossible.
It is an object of the present invention to provide a scheme for the reliable recognition of atoms, molecules, cells, viruses, bacteria, or microorganisms in various environments.
It is an object of the present invention to provide a scheme for the reliable detection of properties of liquids in various environments.
It is an object of the present invention to provide a scheme for the automated control of liquid flows.
It is an object of the present invention to provide a scheme for the smart release or injection of a pharmaceutical substance or the like.
It is an object of the present invention to provide a scheme for transducing molecular recognition, chemical affinity, or physical property into a mechanical response.